Search

Summary: Introduction: Rapidity of effect of advanced therapies for patients with Crohn's disease (CD) can be an essential decision parameter; however, comparative evaluation is lacking. We aimed to compare early response for advanced CD therapies in a network meta‐analysis (NMA). Methods: We searched systematically MEDLINE, Embase, and CENTRAL up to 19 February 2024, for randomised controlled trials. The co‐primary outcomes were induction of clinical remission (Crohn's Disease Activity Index (CDAI) ≤150) and clinical response (≥100‐point reduction in CDAI) within the first 6 weeks of treatment. We incorporated any assessment within this time point in a Bayesian random‐effects NMA following PRISMA‐NMA guidance (PROSPERO ID: CRD42022368509). Results: Twenty‐five studies, comprising 7414 patients, were included. Infliximab combined with azathioprine or monotherapy ranked highest for induction of clinical remission within 6 weeks and was significantly superior to certolizumab, ustekinumab, guselkumab, vedolizumab, and upadacitinib. However, superiority over risankizumab 600 mg and adalimumab 160/80 mg was non‐significant. Accordingly, infliximab in combination with azathioprine and guselkumab 600 mg ranked highest in the corresponding analysis of clinical response with no statistical significance demonstrated. Among bio‐exposed patients, none of whom received infliximab, upadacitinib, and risankizumab induced the highest clinical responses. On the other hand, vedolizumab, certolizumab, and ustekinumab ranked lowest across the analyses. Conclusions: We found infliximab to be ranked highest and superior to all other agents but risankizumab and adalimumab, demonstrating the highest probability of early induction of remission. Upadacitinib and risankizumab induced the highest clinical responses in bio‐exposed patients. However, infliximab was not investigated in this population. [ABSTRACT FROM AUTHOR]

Summary: Background: Vitamin D deficiency is highly prevalent among patients with IBD, however, data on its association with clinical outcomes are conflicting. Aim: To perform a systematic review and meta‐analysis to explore the association of low vitamin D status with clinical outcomes in patients with IBD. Methods: We searched PubMed, Embase, Scopus and Web of Science from inception to February 2018 for observational studies evaluating the association of low 25(OH)D status on IBD disease activity, mucosal inflammation, clinical relapse and quality of life. Odds ratios (ORs) were pooled and analysed using a random effects model. Results: Twenty‐seven studies were eligible for inclusion comprising 8316 IBD patients (3115 ulcerative colitis, 5201 Crohn's disease). Among IBD patients, low 25(OH)D status was associated with increased odds of disease activity (OR 1.53, 95% CI 1.32‐1.77, I2 = 0%), mucosal inflammation (OR 1.25, 95% CI 1.06‐1.47, I2 = 0%), low quality of life (QOL) scores (OR 1.30, 95% CI 1.06‐1.60, I2 = 0%) and future clinical relapse (OR 1.23, 95% CI 1.03‐1.47, I2 = 0%). In subgroup analysis, low vitamin D status was associated with Crohn's disease activity (OR 1.66, 95% CI 1.36‐2.03, I2 = 0%), mucosal inflammation (OR 1.39, 95% CI 1.03‐1.85, I2 = 0%), clinical relapse (OR 1.35, 95% CI 1.14‐1.59, I2 = 0%), and low QOL scores (OR 1.25, 95% CI 1.04‐1.50, I2 = 0%) and ulcerative colitis disease activity (OR 1.47, 95% CI 1.03‐2.09, I2 = 0%) and clinical relapse (OR 1.20, 95% 1.01‐1.43, I2 = 0%). Conclusions: Low 25(OH)D status is a biomarker for disease activity and predictor of poor clinical outcomes in IBD patients. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aims: Inflammatory bowel disease (IBD) may be complicated by primary sclerosing cholangitis (PSC). We aimed to assess the characteristics of Danish PSC‐IBD patients and to compare their prognosis with IBD patients without PSC. Methods: A retrospective nationwide population‐based cohort of 257 PSC‐IBD patients was assessed through Danish national registries and manual scrutiny of patient files. Results: For all PSC‐IBD patients diagnosed after 1976 (n = 222) and 8231 IBD controls (ie, without PSC), the cumulative probability of resective surgery, liver transplantation, cancer, and survival from 1977 through 2011 was estimated and compared by log‐rank test and Cox regression. PSC‐IBD patients primarily had ulcerative colitis (UC) (72%), were diagnosed in young adulthood (median age at IBD diagnosis, 23 years), and 9% were smokers. Among PSC‐UC patients 78% had pancolitis at diagnosis. Among patients with PSC and Crohn's disease (CD) 91% had colonic involvement. The PSC‐IBD patients had a significantly higher probability of receiving resective surgery (HR; 2.13, 95% CI: 1.50‐3.03); of developing colorectal cancer (CRC) (HR; 21.4, 95% CI: 9.6‐47.6), of cholangiocarcinoma (HR; 190, 95% CI: 54.8‐660), and of dying (HR; 4.39, 95% CI: 3.22‐6.00) as compared to non‐PSC‐IBD controls. The 25‐year cumulative risk of liver transplantation was high (53%). Conclusions: This unselected population‐based study shows that PSC‐IBD patients not only have an extensive phenotype of IBD, they are also treated more intensively than other patients with IBD. However, the prognosis remains poor and without any apparent improvement over calendar time. [ABSTRACT FROM AUTHOR]

Use of the immunomodulators thiopurines and methotrexate (MTX) in the treatment of inflammatory bowel disease (IBD), i.e., Crohn's disease and ulcerative colitis (UC), is considered to be good clinical practice. However, despite being administered to a considerable number of IBD patients over the years, questions remain about the most rational treatment regimens of azathioprine (AZA), 6-mercaptopurine (6-MP), and MTX, and results from a range of recent studies necessitate increased attention to how to optimize the use of these immunomodulators. First and foremost, it is of utmost importance to define the subgroup of IBD patients in need of immunomodulators, including those in need of combination therapy with biologic agents, especially because some side effects may be rather severe. Second, colorectal cancer is observed more often in IBD patients than in the background population. However, a recent nationwide Dutch study pointed to a preventive effect of thiopurines. Finally, the need for an appropriate approach to the discontinuation of immunomodulators is emphasized. Since controversy continues regarding the most appropriate use of immunomodulators, this paper is focusing on pharmacokinetics, pharmacogenetics, and therapeutic blood testing, as well as the occurrence of adverse events, when using AZA, 6-MP, and MTX in an attempt to determine a more up-to-date and rational treatment regimen in IBD. [ABSTRACT FROM AUTHOR]

Blau syndrome is a hereditary granulomatous disease caused by mutations in the CARD15 gene that is diagnosed in children of young age with exanthema/erythema, arthritis/periarthritis and/or uveitis. We report two cases of Blau syndrome in Danish Caucasian monozygotic male twins, exhibiting a heterozygous de novo R334W mutation in codon 334 of CARD15. The patients were initially diagnosed as having sarcoidosis. In both twins, symptoms (exanthema, arthritis/periarthritis) started at 1 year of age, and were followed by uveitis at 7–10 years of age. There was no involvement of the lungs or other organs. An initial course of standard antituberculous treatment had no effect on the symptoms. Hydroxychloroquine and cyclosporine A were also ineffective, and the latter caused impaired renal function. Partial symptomatic relief was obtained with prednisolone and increased benefit was observed in combination with methotrexate. Subsequent introduction of the TNF-α inhibitor eternacept did not discernibly benefit the clinical condition, but was associated with recurrent infections. In contrast, a trial of infliximab therapy demonstrated clinical efficacy and eliminated all symptoms, restoring a high quality of life. At follow up at 20 years of age (after 2–5 years of infliximab treatment) the twins had an almost normal physical appearance and a normal psychomotoric development, indicating a favourable short-term prognosis of the disease. Blau syndrome has pathologic, clinical and therapeutic features in common with sarcoidosis, but rarely involves the lungs or other parenchymatous organs. In children, discrimination between early onset sarcoidosis and Blau syndrome should include a CARD15 mutation analysis. [ABSTRACT FROM AUTHOR]